tbuckley/cabot-search huggingface dataset:
Phase II neoadjuvant pyrotinib combined with epirubicin and cyclophosphamide followed by docetaxel in HER2-low–expressing and HR-positive early or locally advanced breast cancer (PILHLE-001): A single-arm trial.
Authors: Yuan Xia, Wenqian Yang, Ya-Ping Yang, Yingying Zhu, Yinduo Zeng, Tao Qin, Shijie Jia, Jiayi Chen, Chang Gong
Journal: Journal of Clinical Oncology (2022)

TPS620 Background: As a latent new subtype, HER2-low-expressing breast cancer has attracted increasing attention. However, HER2-low-expressing/HR-positive early or locally advanced breast cancer (E/LABC) has the lowest pathological complete response (pCR) rate among all types of breast cancer. Pyrotinib, a small-molecule HER1/HER2/HER4 tyrosine kinase inhibitor, combined with chemotherapy regimen showed excellent efficacy and safety in the treatment of patients with HER2-positive early, locally advanced and metastatic breast cancer. In-vitro experiment showed pyrotinib can significantly inhibit colony formation in breast cancer cell lines with different HER2 expression levels including HER2-positive and HER2-low-expressimg [immunohistochemistry (IHC) 2+/in situ hybridization (ISH) negative]. Therefore, the investigator-driven, ongoing PILHLE-001 trial has been conducted to evaluate the potential role of neoadjuvant pyrotinib plus chemotherapy in the treatment of HER2-low-expressing/HR-positive E/LABC, which may provide a novel neoadjuvant therapeutic strategy for these patients. Methods: PILHLE-001, as a single-arm, phase Ⅱ study, is the first trial to evaluate the efficacy and safety of neoadjuvant pyrotinib combine with chemotherapy in HER2-low-expressing (defined as IHC 2+ with ISH negative) and HR-positive (ER or PR &gt; 1% stained cells) E/LABC (cT1c with histologically involved lymph nodes or ≥cT2). Patients who have HER2 IHC 1+, or severe heart diseases or basic gastrointestinal diseases are excluded. The trial has 80% power to detect true difference from previous reported pCR rate of 17.5%, to an expected pCR rate of 35% at two-sided alpha level of 0.05. Considering a drop rate of 10%, a total of 46 patients will be needed. Since May 19, 2021 until now, 19 patients have been enrolled. All eligible patients will receive pyrotinib 320mg orally daily with all chemotherapy cycles (epirubicin 90 mg/m² intravenously plus cyclophosphamide 600 mg/m² intravenously on day 1 for four 3-week cycles followed by docetaxel 100 mg/m² intravenously on day 1 for four 3-week cycle). The primary outcome is the rate of total pCR, defined as no residual invasive tumor cells in the breast and axillary nodes, regardless of ductal carcinoma in situ (ypT0/is ypN0) after neoadjuvant treatment. The secondary outcomes include Miller-Payne grade, residual cancer burden score, overall response rate, breast conservation rate, disease-free survival, overall survival, exploratory biomarkers and drug related safety. Primary efficacy outcomes will be analyzed in the intention‐to‐treat population and safety outcomes in the safety set population. Long-term efficacy outcomes will be assessed later with enough follow-up. Clinical trial information: NCT05165225.
A randomized trial on pelvic lymph node dissection versus no lymph node dissection at radical prostatectomy: Report of a trial in progress.
Authors: Nicole Benfante, Erin Carroll, Jessica Carruthers, Timothy F. Donahue, James Andrew Eastham, Behfar Ehdaie, Alvin C. Goh, Vincent Paul Laudone, Eugene J. Pietzak, Robert Smith, Andrew Vickers, Daniel D. Sjoberg, Peter T. Scardino, Karim A. Touijer
Journal: Journal of Clinical Oncology (2022)

TPS5116 Background: The therapeutic benefit of pelvic lymph node dissection (PLND) in the surgical treatment of localized prostate cancer remains unproven. In this trial we aim to evaluate whether PLND reduces biochemical recurrence rates in clinically localized prostate cancer patients. We are presenting our experience in accrual during our first year of implementing this trial at Memorial Sloan Kettering Cancer Center. Methods: Patients without evidence of positive or suspicious pelvic lymph nodes on pre-operative imaging, and without prior pelvic radiation for prostate cancer are eligible. Following informed consent prior to radical prostatectomy, patients are enrolled onto the trial and surgeons are randomized using a cluster randomization. Surgeons are randomized to perform a PLND vs. no PLND for a 3-month period. Since our trial began accruing in July 2020, we have enrolled 366 patients (51 high risk, 286 intermediate risk, and 29 low risk) out of 996 eligible patients (37%) through January 2022. We have enrolled 168 patients in the PLND arm and 198 patients in the no PLND arm. Table 1 shows the breakdown of patient consent status in each risk group, by randomization assignment. At this stage in the accrual, we do not see evidence of consenting bias among PLND vs. no PLND randomization and risk group. We conclude that a single-center cluster randomized trial can accrue large numbers of patients in a short period of time, allowing for large scale trials to be completed. Currently, our trial is on track to complete accrual within our 5-year goal. Clinical trial information: NCT01407263. [Table: see text]
Case Fatality of Patients With Type 1 Diabetes After Myocardial Infarction
Authors: Anne M. Kerola, Markus Juonala, Antti Palomäki, Anne Grete Semb, Päivi Rautava, Ville Kytö
Journal: Diabetes Care (2022)

Type 1 diabetes is a risk factor for myocardial infarction (MI). We aimed to evaluate the case fatality in patients with type 1 diabetes after MI.
Time to access to novel anticancer drugs in Europe, a case study in seven European countries.
Authors: Colinda Post, Hanneke W.M. Van Laarhoven, Carla Hollak
Journal: Journal of Clinical Oncology (2022)

1586 Background: After European Medicines Agency Marketing Authorization (EMA-MA) different national reimbursement processes may contribute to unequal access throughout the EU. The aim of this study is to investigate the access time to new anticancer medicines in seven high-income Northern European countries and factors influencing the reimbursement process. Methods: We performed a retrospective database study. New anticancer medicines were included with a positive CHMP advice between January 2016 and January 2020, leading to EMA-MA followed by an application for national reimbursement approval in Germany, UK, France, The Netherlands, Belgium, Norway and Switzerland. The relevant Health Technology Assessment (HTA) - and reimbursement websites for each country were used to identify reimbursement dates. Time to access was defined as the time between EMA-MA and date of inclusion in the relevant reimbursement list. In addition we investigated the differences in national approval process and study-, medication- and patient- related factors which might influence the time to reimbursement. Results: We found that for the thirty-six new anticancer medicines, national reimbursement came on average 289 days after EMA-MA, with a variety of -125 in Switzerland (i.e. non EU-member) to 1415 days. Of these EMA-MA new anticancer medicines 42% were reimbursed in all countries. The average number of cancer medicines reimbursed in the examined countries was 27 (75%), with a range of 24 (67%) in Belgium to 36 (100%) in Germany. The shortest average time from EMA-MA to reimbursement were in Germany, 2.33 days, France and Switzerland following with 207 days and 279 days respectively. The median time to reimbursement was 227 days with a range of 3 days in Germany to 553 days in Belgium. In Germany, where there is no pricing and reimbursement approval required when launching a pharmaceutical, 100% of the cancer medicines are reimbursed within five days. After one year, In the UK 56% of the medicines are reimbursed, followed by 53% in the Netherlands, France and Switzerland. Belgium and Norway have a one year reimbursement rate of 14% and 11% respectively. Access to anticancer medicines is dependent on regulatory procedures, HTA and price regulations. Germany has a fast market access for anticancer medicines with a price regulation one year after launching the medicines. In the other countries, price regulation is part of the launching process. Other factors which might accelerate the time to reimbursement we are examining are high clinical benefit score (ESMO-MCBS), (non-)orphan status of the medicines and submission by big pharmaceuticals. Conclusions: This study shows that after EMA-MA, except for Germany, on average it takes a long time for anticancer medicines to be reimbursed in Northern European countries. There is a considerably variety both within and among countries.
Treatment With Adjuvant Abemaciclib Plus Endocrine Therapy in Patients With High-risk Early Breast Cancer Who Received Neoadjuvant Chemotherapy
Authors: Miguel Martin, Roberto Hegg, Sung-Bae Kim, Michael Schenker, Daniela Grecea, Jose Angel Garcia-Saenz, Konstantinos Papazisis, QuChang Ouyang, Aleksandra Lacko, Berna Oksuzoglu, James Reeves, Meena Okera, Laura Testa, Chikako Shimizu, Neelima Denduluri, Hryhoriy Adamchuk, Shaker Dakhil, Ran Wei, Tammy Forrester, Maria Munoz Fernandez, Annamaria Zimmermann, Desiree Headley, Stephen R. D. Johnston
Journal: JAMA Oncology (2022)

Patients selected to receive neoadjuvant chemotherapy (NAC) are usually those at higher risk of relapse, and there is a need to find better therapeutic options for these patients.
Preliminary analysis of an expanded access study of the fixed-dose combination of pertuzumab (P) and trastuzumab (H) for subcutaneous injection (PH FDC SC) for at-home administration (admin) in patients (pts) with HER2-positive (HER2+) breast cancer (BC) during the COVID-19 pandemic.
Authors: Chau T. Dang, Sara M. Tolaney, Fauzia Riaz, Antoinette R. Tan, Katherine H. R. Tkaczuk, Anthony Francis Yu, Jennifer Liu, Anita M. Fung, Anna Yang, Bann-mo Day, Hope S. Rugo
Journal: Journal of Clinical Oncology (2022)

1515 Background: Standard of care for HER2+ early/first-line metastatic BC (EBC/MBC) is P + H and concurrent chemotherapy (CT); PH FDC SC offers faster, more convenient admin vs intravenous (IV) P + H. COVID-19 has caused unprecedented strain on healthcare systems and disruption to cancer care; treatment (Tx) at home may: enable pts to continue cancer Tx; reduce exposure to COVID-19; free up hospital resources. This study’s main objectives: to enable continuity of care during COVID-19; to assess safety of PH FDC SC given at home. Methods: This is an ongoing single-arm, hybrid, decentralized clinical trial (NCT04395508). Pts with HER2+ EBC/MBC who completed concurrent CT with P + H IV and are receiving/about to receive maintenance P + H IV, PH FDC SC, or H SC are switched to PH FDC SC given at home by a home health nursing provider (HHNP) until disease progression, unacceptable toxicity, pt withdrawal, or physician recommendation (pts with EBC will complete ≤18 cycles). The study endpoint is safety. A subset of pts took part in HARRIET, a substudy of at-home cardiac surveillance with artificial intelligence-guided cardiac ultrasound and optional 6L ECG acquired by an HHNP. Results: Data for 114 pts (1 male) were available at cutoff (Jan 19, 2022): 18 (16%) completed Tx; 20 (18%) discontinued; 76 (67%) remain on study; 79 (69%) had a COVID-19 vaccine while on study. Median age was 49 years; pts were balanced between EBC (n = 55, 48%) and MBC (n = 59, 52%); received a median of 6 (EBC) and 8 (MBC) cycles; and were from metropolitan (n = 109), urban (n = 4), and rural (n = 1) areas. 11 pts tested COVID-19-positive during the Tx phase: 8 continued Tx after appropriate COVID-19 Tx and/or quarantine. Safety is summarized in the table. No new adverse events (AEs) emerged due to home admin. AEs of special interest were grade (gr) 1–2: admin-related reactions (n = 76, 67%), hypersensitivity (n = 5, 4%), cardiac dysfunction (n = 4, 4%), except 1 case of gr ≥3 diarrhea. AEs leading to study Tx discontinuation or interruption/dose reduction occurred in 3 (3%) and 15 (13%) pts. A subset of 7 pts completed at-home cardiac surveillance testing; quantitative assessment of left ventricular ejection fraction was feasible in 3 (43%); 5 (71%) preferred at-home surveillance to clinic. Conclusions: In this preliminary analysis, safety of PH FDC SC at home was consistent with the established P + H safety profile, indicating that PH FDC SC at home is a viable option for continuing BC care during and beyond COVID-19. Clinical trial information: NCT04395508. [Table: see text]
International Olympic Committee (IOC) consensus statement on acute respiratory illness in athletes part 2: non-infective acute respiratory illness
Authors: Martin Schwellnus, Paolo Emilio Adami, Valerie Bougault, Richard Budgett, Hege Havstad Clemm, Wayne Derman, Uğur Erdener, Ken Fitch, James H Hull, Cameron McIntosh, Tim Meyer, Lars Pedersen, David B Pyne, Tonje Reier-Nilsen, Wolfgang Schobersberger, Yorck Olaf Schumacher, Nicola Sewry, Torbjørn Soligard, Maarit Valtonen, Nick Webborn, Lars Engebretsen
Journal: British Journal of Sports Medicine (2022)

Acute respiratory illness (ARill) is common and threatens the health of athletes. ARill in athletes forms a significant component of the work of Sport and Exercise Medicine (SEM) clinicians. The aim of this consensus is to provide the SEM clinician with an overview and practical clinical approach to non-infective ARill in athletes. The International Olympic Committee (IOC) Medical and Scientific Committee appointed an international consensus group to review ARill in athletes. Key areas of ARill in athletes were originally identified and six subgroups of the IOC Consensus group established to review the following aspects: (1) epidemiology/risk factors for ARill, (2) infective ARill, (3) non-infective ARill, (4) acute asthma/exercise-induced bronchoconstriction and related conditions, (5) effects of ARill on exercise/sports performance, medical complications/return-to-sport (RTS) and (6) acute nasal/laryngeal obstruction presenting as ARill. Following several reviews conducted by subgroups, the sections of the consensus documents were allocated to ‘core’ members for drafting and internal review. An advanced draft of the consensus document was discussed during a meeting of the main consensus core group, and final edits were completed prior to submission of the manuscript. This document (part 2) of this consensus focuses on respiratory conditions causing non-infective ARill in athletes. These include non-inflammatory obstructive nasal, laryngeal, tracheal or bronchial conditions or non-infective inflammatory conditions of the respiratory epithelium that affect the upper and/or lower airways, frequently as a continuum. The following aspects of more common as well as lesser-known non-infective ARill in athletes are reviewed: epidemiology, risk factors, pathology/pathophysiology, clinical presentation and diagnosis, management, prevention, medical considerations and risks of illness during exercise, effects of illness on exercise/sports performance and RTS guidelines.
Responses to salvage therapy in AL amyloidosis after progression on daratumumab.
Authors: Hashim Mann, Yana Salei, Teresa Fogaren, Denis Toskic, Stephanie Scalia, Xun Ma, Ping Zhou, Ray Comenzo
Journal: Journal of Clinical Oncology (2022)

e20030 Background: Daratumumab (Dara)-based therapy is the standard for upfront treatment in systemic light-chain (AL) amyloidosis and is preferred in the relapsed setting. However, outcomes of patients who relapse on dara remain unclear. In such circumstances, optimal sequencing of subsequent drugs is also not well-established. Here, we describe outcomes of AL patients who progressed on dara-based treatments. Methods: We conducted a retrospective review of AL patients treated at our center from 2015 to 2022. Patients were eligible if they progressed on dara at any time during disease course. We recorded all standard metrics, including serologic and biomarker data. Patients with incomplete follow-up or missing data were excluded. Descriptive statistics were performed with Prism 5.0 (GraphPad; San Diego, CA). Results: A total of 11 patients were identified. Median age was 73. Nine were male, and 8 had AL, λ-type (2–κ, 1–heavy chain). Median iFLC at baseline was 342 mg/L (55.6–9780) and NT-proBNP was 1166 pg/mL (147–5000). Cardiac involvement was most common (82%); 64% had ≥2 organs involved. Six had t(11;14) by FISH and/or cyclin D1 overexpression by IHC, 3 had gain 1q, 2 had del 17p, and 4 had complex cytogenetics. Five patients received ≥2 prior lines of therapy, including 3 ASCT. Three (27%) received dara in induction, whereas the most common indications for later use were hematologic/organ progression (45%), suboptimal response (18%), and refractory disease (9%). At a median follow-up of 82 weeks, all patients had progressed. Median time to next therapy was 15 weeks (7–151). Six (55%) continued dara at salvage, while other agents used were bortezomib (n=5), ixazomib (n=6), pomalidomide (n=5), cyclophosphamide (n=4), bendamustine (n=4), and belantamab mafodotin (n=3). All patients with t(11;14) or cyclin D1 overexpression received venetoclax, of whom 4 also received HMG-CoA reductase inhibitors (statins). ORR was 100%. Hematologic VGPR and CR rates were each 36%, PR 18%, and 1 patient had low dFLC PR. Rate of VGPR or better was higher in patients with t(11;14) and/or cyclin D1 overexpression (83% vs 60%; P=0.55). Of the 4 patients who received venetoclax and statins for t(11;14) disease, 3 had CR and 1 had VGPR. One renal and 3 cardiac responses were observed. At last follow-up, 2 patients with VGPR had died while the rest had ongoing responses. Conclusions: In our study, most patients had t(11;14) and progressed on dara within 20 weeks. Salvage therapy incorporating novel agents yielded impressive responses. The combination of venetoclax and statins was effective in overcoming the negative impact of t(11;14) although further studies are needed for validation.[Table: see text]
Click chemistry extracellular vesicle/peptide/chemokine nanocarriers for treating central nervous system injuries
Authors: Huitong Ruan, Yongfang Li, Cheng Wang, Yixu Jiang, Yulong Han, Yiwei Li, Dandan Zheng, Jing Ye, Gang Chen, Guo-yuan Yang, Lianfu Deng, Ming Guo, Xingcai Zhang, Yaohui Tang, Wenguo Cui
Journal: Acta Pharmaceutica Sinica B (2022)

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.
The value of pretreatment <sup>18</sup>F-FDG PET/CT to predict the pathological treatment response of hepatocellular carcinoma patients treated with PD-1 inhibitors and lenvatinib as a conversion therapy in BCLC stage C.
Authors: Guanyun Wang, Guangyu Ma, Wenwen Zhang, Baixuan Xu, Shichun Lu, Jiaxin Chen, Xiaohui Luan, Zhanbo Wang, Xiaodan Xu, Zhiwei Guan, Shuang Tong
Journal: Journal of Clinical Oncology (2022)

e16130 Background: Current systemic therapy for patients with hepatocellular carcinoma (HCC) in BCLC stage C consists of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). This study aimed to assess the parameters of pretreatment 18 F-FDG PET/CT as a predictor of the pathological treatment response (PTR) of HCC patients treated with PD-1 inhibitors and lenvatinib as a conversion therapy in BCLC stage C. Methods: We retrospective analyzed 20 consecutive patients with HCC in BCLC stage C. All patients underwent pretreatment 18 F-FDG PET/CT and treated with PD-1 inhibitors and lenvatinib as a conversion therapy and surgery. Patients were categorized into responders (n=9) and non-responders (n=11) according to PTR. The PTR was classified based on the primary tumor cellularity (responder, defined as &lt;10% cellularity). The parameters of PET/CT including lesion size, SUVmax (max standardized uptake value), SUVmean (mean standard uptake value), MTV 2.5 (metabolic tumor volume 2.5 ), TLG 2.5 (total lesion glycolysis 2.5 ), SUVpeak (peak standard uptake value), and TLR (tumor-to-normal liver standardized uptake value ratio, SUVmax of the tumor/SUVmean of the normal liver parenchyma) were calculated and compared between two groups. The diagnostic efficacy was evaluated by ROC. PTR was compared with pretreatment 18 F-FDG PET/CT parameters by using Spearman correlation analysis. The prognosis was followed up. Results: TLR (5.59±1.90 vs. 2.84±1.70, respectively; P=0.003) showed significant difference in responders and non-responders and the largest area under the curve (sensitivity: 1.000, specificity: 0.727, positive predictive value: 0.750, negative predictive value: 1.000, AUC=0.899, 95%CI: 0.759-1.000), and optimal diagnostic threshold of 3.09. The relationship between 18 F-FDG PET/CT parameters and PTR showed TLR had moderate positive correlation with pathological treatment response, with correlation coefficients (rs) of 0.69 ( P＜0.05). During the follow-up, no patients died, and 1 patient (11.1%) showed tumor recurrence in responders. In all 11 non-responders, 5 patients (45.5%) had tumor recurrence and 4 patients (36.4%) died. Conclusions: The TLR may be a powerful marker to predict the PTR of HCC patients with BCLC stage C who treated with PD-1 inhibitors and lenvatinib as a conversion therapy.[Table: see text]